Method of manufacturing a PTP sheet for packaging a pharmaceutical drug

ABSTRACT

A method of manufacturing a PTP sheet for pharmaceutical drug packaging from which a solid pharmaceutical drug is easily taken out and in which a pocket portion is hard to be accidentally damaged. The PTP sheet has a first sheet from which a pocket portion capable of housing a solid pharmaceutical drug protrudes to the side of an upper surface and a second sheet which is stuck to a lower surface of the first sheet and which closes an opening of the pocket portion. The pocket portion has a peripheral wall portion having a peripheral surface continuous with the upper surface and a top portion having a top surface continuous with the peripheral surface of the peripheral wall portion. A wall thickness of the peripheral wall portion is smaller than a wall thickness of the top portion.

CROSS REFERENCE TO RELATED APPLICATION

This is a continuation of U.S. patent application Ser. No. 15/316,371 ofNipro Corporation (first named inventor Kazuaki Uetake) filed on Dec. 6,2016 for “PTP Sheet for Drug Packaging,” based on PCT Application No.PCT/JP2015/066180 filed on Jun. 4, 2015.

BACKGROUND OF THE INVENTION

The present invention relates to a PTP sheet for pharmaceutical drugpackaging.

PTP (Press Through Package) packaging has been widely used for packagingsolid pharmaceutical drugs, such as tablets and capsule agents, in thefield of packaging of pharmaceutical products. A PTP sheet forpharmaceutical drug packaging is manufactured by molding pockets eachhousing a solid pharmaceutical drug in a resin film, loading the solidpharmaceutical drug in each pocket, and then sticking a sheet containingaluminum foil or the like to the resin film to seal the pockets. Whenthe solid pharmaceutical drug loaded in the pocket portion is pressedtogether with the pocket by a user, the sheet is broken by the solidpharmaceutical drug, so that the solid pharmaceutical drug can be takenout.

CITATION LIST Patent Literature

Patent Literature 1: Japanese Unexamined Patent Application PublicationNo. 2012-106771

Patent Literature 2: Japanese Unexamined Patent Application PublicationNo. 2008-100690

Patent Literature 3: Japanese Unexamined Patent Application PublicationNo. 2008-68873

Patent Literature 4: Japanese Unexamined Patent Application Publication(Translation of PCT Application) No. 11-513641

SUMMARY OF THE INVENTION

In order to easily take out a solid pharmaceutical drug from a pocket ofa PTP sheet for pharmaceutical drug packaging, it is desirable that thepocket is easily pressed and broken by a user. For example, when thepocket is produced in a resin sheet by vacuum molding, the wallthickness of the peripheral wall of the pocket tends to be thick.Therefore, the peripheral wall of the pocket is hard to be deformed, sothat the pocket is hard to be pressed and broken. In particular, usershaving relatively weak hand or finger force, such as elderly persons orchildren, may be difficult to take out a solid pharmaceutical drug fromthe PTP sheet for pharmaceutical drug packaging. On the other hand, whena resin film is made thin so that the pocket is easily deformed, thepocket may be damaged by accidently applied external force intransportation or storage.

The present invention has been made in view of the above-describedcircumstances. It is an object of the present invention to provide a PTPsheet for pharmaceutical drug packaging from which a solidpharmaceutical drug is easily taken out and in which a pocket portion ishard to be accidentally damaged.

Solution to the Problem

(1) A PTP sheet for pharmaceutical drug packaging according to thepresent invention has a first sheet from which a pocket portion capableof housing a solid pharmaceutical drug is protruded to a side of a firstsurface which is either a front surface or a back surface and a secondsheet which is stuck to a second surface opposite to the first surfacein the first sheet and which closes an opening of the pocket portion.The pocket portion has a peripheral wall portion having a third surfacecontinuous with the first surface and a top portion having a fourthsurface continuous with the third surface of the peripheral wallportion. The wall thickness of the peripheral wall portion is smallerthan the wall thickness of the top portion.

The wall thickness of the peripheral wall portion of the pocket portionis smaller than the wall thickness of the top portion. Therefore, due tothe fact that a user presses the top portion of the pocket portiontoward the second sheet, the peripheral wall portion is deformed, sothat the pocket portion is pressed and broken. The pocket portion ispressed and broken and, simultaneously therewith, the solidpharmaceutical drug housed in the pocket portion ruptures the secondsheet. On the other hand, since the wall thickness of the top portion ofthe pocket portion is relatively thick, the top portion is hard to bedamaged even when a sharp substance collides with the top portion.

(2) Preferably, a partial region of the first sheet is heated, and thena region containing the partial region is sucked into a decompressedconcave portion, whereby the pocket portion is molded.

The partial region is heated in the process where the pocket portion ismolded by so-called vacuum molding. Therefore, when the first sheet issucked into the concave portion, the partial region more easily extendsand the thickness more easily decreases as compared with the otherregion.

(3) Preferably, the partial region is a region corresponding to theperipheral wall portion.

Thus, the thickness of the peripheral wall portion of the pocket portioncan be made smaller than the thickness of the top portion by vacuummolding. The top portion of the pocket portion is not heated and is hardto be extended in such a manner that the wall thickness decreases invacuum molding. Therefore, the transparency of the top portion isimproved. Thus, a stamp and the like of the solid pharmaceutical drughoused in the pocket portion can be easily visually recognized throughthe top portion.

(4) Preferably, the outer shape of the pocket portion is a cylindricalshape.

(5) Preferably, the main component of the first sheet is a thermoplasticresin.

(6) Preferably, the second sheet contains aluminum as the maincomponent.

(7) Preferably, the wall thickness of the peripheral wall portion is 40to 160 μm and the wall thickness of the top portion is 200 to 400 μm.

Advantageous Effects of the Invention

According to the present invention, the wall thickness of the peripheralwall portion of the pocket portion is smaller than the wall thickness ofthe top portion, and therefore a solid pharmaceutical drug is easilytaken out from the pocket portion and the top portion is hard to beaccidentally damaged. Moreover, the transparency of the top portion ofthe pocket portion is improved, so that the solid pharmaceutical drughoused in the pocket portion can be easily visually recognized throughthe top portion.

BRIEF DESCRIPTION OF DRAWINGS

FIGS. 1A-1B are perspective views of the appearance of a PIP sheet 10housing solid pharmaceutical drugs 11, in which FIG. 1A illustrates astate where the PTP sheet 10 is viewed from diagonally above and FIG. 1Billustrates a state where the PTP sheet 10 is viewed from diagonallybelow.

FIG. 2 is an enlarged cross sectional view of a pocket portion 16 of thePTP sheet 10.

FIG. 3 is an enlarged cross sectional view in a state where the pocketportion 16 is pressed and broken and the second sheet 15 is ruptured.

FIG. 4A is a view illustrating a first sheet 14 in a state before thepocket portion 16 is formed by vacuum molding and FIG. 4B is a viewillustrating the first sheet 14 in a state where the pocket portion 16is formed by vacuum molding.

FIGS. 5A, 5B, and 5C are views illustrating modifications of a heatingplug 52.

DESCRIPTION OF THE PREFERRED EMBODIMENT

Hereinafter, an embodiment of the present invention is describedreferring to the drawings as appropriate. The embodiment described belowis merely an example of the present invention. It is a matter of coursethat the embodiment of the present invention can be altered asappropriate in the range where the scope of the invention is notaltered. In the following description, an up-and-down direction 5 isdefined on the basis of a state where the PTP sheet 10 is disposed withthe surface in which the pocket portions 16 are formed upside, thelateral direction in the surface described above is defined as a forwardand backward direction 6, and a direction perpendicular to theup-and-down direction 5 and the forward and backward direction 6 isdefined as a left and right direction 7.

[Schematic Configuration of PTP Sheet 10]

As illustrated in FIGS. 1A and 1B, the PTP sheet 10 (an example of thePTP sheet for pharmaceutical drug packaging) is an approximatelyrectangular sheet as viewed in plan. The shape of the PTP sheet 10 isnot limited to the rectangular shape. For example, the PTP sheet 10 maybe a square shape, a rhombus shape, a round shape, or the like as viewedin plan.

As illustrated in FIG. 2, a solid pharmaceutical drug 11, such as atablet or a capsule agent, is sealed in the pocket portion 16 in the PTPsheet 10. The dimension in the forward and backward direction 6 and theleft and right direction 7 of the PTP sheet 10 can be determined asappropriate depending on the number and the size of the solidpharmaceutical drugs 11 sealed in one PTP sheet 10.

The PTP sheet 10 is configured so that five cells 12, which aredivisions each sealing two solid pharmaceutical drugs 11, are arrangedin the left and right direction 7. In one PTP sheet 10 illustrated inFIGS. 1A and 1B, ten solid pharmaceutical drugs 11 in total are sealed.It is a matter of course that the number of the solid pharmaceuticaldrugs 11 to be sealed in the PTP sheet 10 is not limited to ten pieces.

On the right side of the cell 12 on the rightmost side, a cell 21 inwhich the solid pharmaceutical drug 11 is not sealed is provided. Thecell 21 is used as a region for holding the PTP sheet 10 by a user, aregion for writing down or printing information on the solidpharmaceutical drug 11, or the like. The position where the cell 21 isprovided is not limited to the right side of the cell 12 on therightmost side, may be located on the left side of the cell 12 on theleftmost side or may be located between the two cells 12, or the cell 21may not be provided in the PTP sheet 10.

The first sheet 14 has slits 13 formed on the boundary between the cells12 and on the boundary of the cells 12 and 21. The PTP sheet 10 can bedivided into one unit of the cells 12 and 21 by being bent along theslit 13 by the hands of a pharmacist or a patient. The dimensions in theforward and backward direction 6 and the left and right direction 7 ofthe cells 12 can be determined as appropriate depending on the numberand the size of the solid pharmaceutical drugs 11 to be sealed in thecells 12. The dimensions in the forward and backward direction 6 and theleft and right direction 7 of the cell 21 can be determined asappropriate depending on the amount or the like of information which isto be written down in the cell 21.

The PTP sheet 10 is one in which the first sheet 14 which is athermoplastic resin and a second sheet 15 which is a laminated sheet inwhich an aluminum sheet and a resin sheet are laminated on each otherare stuck to each other. The solid pharmaceutical drugs 11 are housed inthe pocket portions 16 formed in the first sheet 14. The openings of thepocket portions 16 are closed with the second sheet 15. The pocketportion 16 of the first sheet 14 is pressed by the finger of a user, andthus the solid pharmaceutical drug 11 presses and breaks the secondsheet 15, whereby the solid pharmaceutical drug 11 packaged in the PTPsheet 10 can be taken out from the pocket portion 16.

Hereinafter, each constituent member of the PTP sheet 10 is described indetail. In the following description, the upper surface and the lowersurface of each sheet are defined based on the up-and-down direction 5described above. An upper surface 31 of the first sheet 14 is equivalentto the first surface and a lower surface 32 of the first sheet 14 (seeFIG. 2) is equivalent to the second surface. The up-and-downrelationship of the upper surface and the lower surface in the followingdescription is a relative relationship determined for convenience ofdescription and the up-and-down relationship of the upper surface andthe lower surface may be reversed.

[First Sheet 14]

As illustrated in FIGS. 1A, 1B, and 2, the first sheet 14 is a sheetobtained by vacuum molding a thermoplastic resin. Examples of thethermoplastic resin include polypropylene (PP), polyvinyl chloride(PVC), polyethylene terephthalate (PET), cyclic polyolefin (COC, COP),or the like, for example. In order to increase the visibility of thesolid pharmaceutical drug 11 housed in the pocket portion 16, one havinghigh transparency is preferable. The first sheet 14 may have a laminatedstructure in which two or more kinds of resin layers are laminated. Thefirst sheet 14 may not necessarily contain only the thermoplastic resinand may be a sheet molded from a resin composition containing athermoplastic resin as the main component. The thickness of asheet-shaped portion other than the pocket portions 16 in the firstsheet 14 varies depending on the type of the resin to be used and ispreferably within the range of 200 μm to 400 μm.

The slits 13 are formed on the boundary between the cells 12. The slits13 are formed on the side of the upper surface 31 of the first sheet 14and are approximately V-shaped grooves in the cross sectional shapeorthogonal to the upper surface 31. The depth along the up-and-downdirection 5 of the slit 13 is slightly longer than half of the thicknessof the first sheet 14. The slits 13 may be perforations in which minuteholes are periodically formed. Or, the slits 13 may be those in whichgrooves and perforations are superimposed. In a manufacturing stage ofthe PTP sheet 10, rollers having a blade on the peripheral edge arerelatively moved in a state of being pressed against the upper surface31 of the first sheet 14, whereby the slits 13 are formed in the firstsheet 14.

Two pocket portions 16 are formed in each cell 12 of the first sheet 14.The outer shape of the pocket portion 16 is an approximately cylindricalshape in which the pocket portion 16 protrudes to the side of the uppersurface 31 of the first sheet 14. The solid pharmaceutical drug 11 ishoused in the internal space formed by the pocket portion 16 in the sideof the lower surface 32 of the first sheet 14. The side of the lowersurface 32 of the pocket portion 16 is an opening through which thesolid pharmaceutical drug 11 is inserted or taken out. The shape, thecapacity of the internal space, the size of the opening, and the like ofthe pocket portion 16 are determined as appropriate corresponding to theouter dimension, capacity, and the like of the solid pharmaceutical drug11. For example, when the solid pharmaceutical drug 11 is a capsuletablet, the pocket portion 16 may have an oval dome shape as viewed inplan.

As illustrated in FIG. 2, the pocket portion 16 has a peripheral wallportion 17 having a peripheral surface 33 (equivalent to the thirdsurface) continuous with the upper surface 31 and a top portion 18having a top surface 34 (equivalent to the fourth surface) continuouswith the peripheral surface 33. The peripheral surface 33 is a surfaceforming the side peripheral surface of the cylindrical-shaped pocketportion 16 and is orthogonal to the upper surface 31 or crosses theupper surface 31 at an angle of almost 90°. The top surface 34 is asurface forming the upper end surface of the cylindrical-shaped pocketportion 16 and is almost parallel to the upper surface 31 and has a domeshape having a center portion swollen upward.

A wall thickness d1 of the peripheral wall portion 17 is smaller than awall thickness d2 of the top portion 18. Specifically, it is preferablethat, when the thickness (wall thickness) of the sheet of a portionother than the pocket portions 16 in the first sheet 14 is about 200 μmto 400 μm, the wall thickness of the peripheral wall portion 17 is 40 to160 μm and the wall thickness of the top portion 18 is 200 to 400 μm.

The pocket portion 16 is vacuum molded as follows. As illustrated inFIG. 4A, the first sheet 14 before the pocket portion 16 is molded is aflat sheet having a fixed thickness. On the side of the upper surface 31of the flat first sheet 14, a die 50 having a concave portion 51 havingthe shape of the pocket portion 16 is disposed, and then, a heating plug52 is disposed at a position which is located on the side of the lowersurface 32 of the first sheet 14 and faces the concave portion 51. Theheating plug 52 has an annular-shaped end surface 53. A portion on theinner side relative to the end surface 53 is cylindrical-shaped spacedepressed from the end surface 53. The end surface 53 corresponds to thepartial region 19 of the first sheet 14 serving as the peripheral wallportion 17 of the pocket portion 16. The partial region 19 and theperipheral wall portion 17 may not necessarily correctly correspond toeach other and, for example, the partial region 19 may not form theentire peripheral wall portion 17 but form a part of the peripheral wallportion 17.

As illustrated in FIG. 4A, the partial region 19 of the flat first sheet14 is heated by the approach of the end surface 53 of the heating plug52. The heating temperature of the partial region 19 by the heating plug52 varies depending on a resin to be used as the first sheet 14 and ispreferably about 120 to 150° C.

As illustrated in FIG. 4B, the partial region 19 is heated, and then theinside of the concave portion 51 of the die 50 is decompressed. Althoughnot illustrated in FIG. 4A or 4B, the concave portion 51 has an openingof an airflow passage through which gas passes. Due to the fact that theair in the concave portion 51 is sucked out from the opening, theconcave portion 51 is decompressed. In connection with the decompressionof the concave portion 51, the first sheet 14 which approaches orcontacts the concave portion 51 is sucked into the concave portion 51 tobe molded following the shape of the concave portion 51. Herein, thepartial region 19 heated as compared with the other region of the firstsheet 14 extends as compared with the other region, so that the wallthickness decreases. Thus, the pocket portion 16 is molded in which thewall thickness of the peripheral wall portion 17 is smaller than thewall thickness of the top portion 18.

[Second Sheet 15]

The second sheet 15 is a laminated sheet in which an aluminum sheet islaminated in such a manner as to be sandwiched between resin sheets. Oneof the resin sheets is an acrylic resin and the other one is a vinylchloride resin. The second sheet 15 may contain only the aluminum sheetor may be a metal sheet other than aluminum. The sheet to be used as alaminated sheet may be resin other than the acrylic resin or the vinylchloride resin. When thermally fused with the first sheet 14, the vinylchloride resin is preferable. When characters, signs, and the like areprinted, the acrylic resin is preferable. The second sheet 15 may be aresin sheet not containing metal sheets insofar as the airtightness ofthe pocket portion 16 is securable to some extent.

As illustrated in FIGS. 1A, 1B, and 2, the second sheet 15 is stuck tothe lower surface 32 of the first sheet 14 in a state where the solidpharmaceutical drug 11 is housed in the pocket portion 16. The openingof the pocket portion 16 is closed by the second sheet 15, so that thesolid pharmaceutical drug 11 is held in the internal space of the pocketportion 16.

As illustrated in FIG. 3, when the solid pharmaceutical drug 11 is takenout from the PTP sheet 10, the pocket portion 16 is pressed with thefinger of a user. Thus, the peripheral wall portion 17 of the pocketportion 16 is deformed in such a manner as to be bent, so that thepocket portion 16 is pressed and broken and, simultaneously therewith,the solid pharmaceutical drug 11 pressed through the top portion 18ruptures the second sheet 15. Then, the solid pharmaceutical drug 11 canbe taken out from the opening of the pocket portion 16 through thesecond broken sheet 15.

The thickness of the second sheet 15 is a thickness which allows thebreakage of the second sheet 15 by the fixed pressing force from thesolid pharmaceutical 11. The thickness of the second sheet 15 isdetermined as appropriate depending on the raw materials of the secondsheet 15, the hardness 11 of the solid pharmaceutical drug 11, e.g.,whether the solid pharmaceutical drug 11 is a tablet or a capsule agent,and the like, for example. The thickness of the second sheet 15 ispreferably within the range of 20 μm to 25 μm.

The second sheet 15 is thermocompression bonded to the first sheet 14 inwhich the solid pharmaceutical drugs 11 are housed in the pocketportions 16. The first sheet 14 and the second sheet 15 pass throughspace between a roller pair, which is mounted in an apparatus formanufacturing the PTP sheet 10 and one roller of which is heated, whilebeing brought into pressure contact with each other by the roller pairin the state where the first sheet 14 and the second sheet 15 areoverlapped with each other. Thus, the first sheet 14 and the secondsheet 15 are thermocompression bonded to each other. Knurls may beformed in the surface of one roller of the roller pair, then fineirregularities having a mesh pattern formed by the knurls may be formedin the second sheet 15. Means sticking the first sheet 14 and the secondsheet 15 to each other is not limited to those described above.

Operational Effects of this Embodiment

According to this embodiment, the wall thickness d1 of the peripheralwall portion 17 of the pocket portion 16 is smaller than the wallthickness d2 of the top portion 18. Therefore, due to the fact that auser presses the top portion 18 of the pocket portion 16 toward thesecond sheet 15, the peripheral wall portion 17 is deformed and thepocket portion 16 is pressed and broken. The pocket portion 16 ispressed and broken and, simultaneously therewith, the solidpharmaceutical drug 11 housed in the pocket portion 16 ruptures thesecond sheet 15. On the other hand, since the wall thickness d2 of thetop portion 18 of the pocket portion 16 is relatively large, the topportion 18 is hard to be damaged even when a sharp substance collideswith the top portion 18.

Moreover, the partial region 19 of the first sheet 14 is heated by theheating plug 52 in the process where the pocket portion 16 is molded byso-called vacuum molding. Therefore, when the first sheet 14 is suckedinto the concave portion 51 of the die 50, the partial region 19 moreeasily extends and the thickness more easily decreases as compared withthe other region.

Moreover, since the partial region 19 of the first sheet 14 is a regioncorresponding to the peripheral wall portion 17, the thickness of theperipheral wall portion 17 of the pocket portion 16 can be made smallerthan the thickness of the top portion 18 by vacuum molding.

Moreover, the top portion 18 of the pocket portion 16 is not heated bythe heating plug 52 and is hard to be extended in such a manner that thewall thickness d2 decreases in vacuum molding, and therefore thetransparency of the top portion 18 is improved. Thus, a stamp and thelike of the solid pharmaceutical drug 11 housed in the pocket portion 16can be easily visually recognized through the top portion 18.Modifications

The shape of the portion on the inner side relative to the end surface53 may be changed as appropriate insofar as the heating plug 52 whenforming the pocket portions 16 in the first sheet 14 in vacuum moldinghas the annular-shaped end surface 53. For example, the cross-sectionalshape of the depressed portion inside the end surface 53 may have atrapezoid shape, a shallow lens shape, or a deep lens shape asillustrated in FIGS. 5A to 5C, respectively. In the rectangular shapeaccording to the embodiment described above or a trapezoid shape (FIG.5A) in Comparative Example in which the depth of the cross-sectionalshape inside the end surface 53 is relatively deep, heat is hard to betransmitted to the inside of the end surface 53 in the heating plug 52,which results in the fact that the wall thickness of the peripheral wallportion 17 of the pocket portion 16 decreases and the wall thickness ofthe top portion 18 increases. On the other hand, in the lens shapes(FIGS. 5B and 5C) in which the depth of the cross-sectional shape insidethe end surface 53 is relatively shallow, heat is easily transmitted tothe inside of the end surface 53 in the heating plug 52, which resultsin the fact that the wall thickness of the peripheral wall portion 17 ofthe pocket portion 16 decreases but the wall thickness of a peripheralportion of the top portion 18, i.e., the vicinity of the boundary withthe peripheral wall portion 17, also decreases.

Moreover, although the first sheet 14 is obtained by vacuum molding athermoplastic resin in the embodiment described above but the firstsheet 14 may be molded by molding methods other than the vacuum molding.For example, after the partial region 19 of the first sheet 14 is heatedby the heating plug 52, the pocket portions 16 may be molded by pressmolding by male and female dies.

EXAMPLES Example 1

Using a resin sheet in which polypropylene (PP) and cyclic polyolefin(COC) were laminated as the first sheet 14 and using a laminated sheetin which an aluminum sheet and a resin sheet were laminated as thesecond sheet 15, the first sheet 14 was heated to about 150° C. usingthe heating plug 52 (in which the cross-sectional shape is a trapezoidshape: see FIG. 5A) described in the modification described above tomanufacture a PTP sheet 10 by vacuum molding.

Examples 2 and 3

PTP sheets 10 were manufactured in the same manner as in Example 1,except using the heating plugs 52 (see FIGS. 5B and 5C) described in themodification described above. More specifically, the PTP sheet 10 inwhich the cross-sectional shape of the depressed portion inside the endsurface 53 of the heating plug 52 had a shallow lens shape (see FIG. 5B)was the PTP sheet 10 of Example 2 and the PTP sheet 10 in which thecross-sectional shape had a deep lens shape (see FIG. 5C) was the PTPsheet 10 of Example 3.

COMPARATIVE EXAMPLE

A PTP sheet 10 was manufactured in the same manner as in Example 1,except using a heating plug not having a portion where the end surfaceof the heating plug is depressed inside and capable of heating theperipheral wall portion 17 and the top portion 18 of the pocket portion16 as a whole.

[Measurement of Thickness of Pocket Portion 16]

The wall thickness of the peripheral wall portion 17 and the top portion18 of the pocket portion 16 of each of the PTP sheets 10 according toExamples 1 to 3 and Comparative Example was measured. For themeasurement, a high-precision laser displacement meter (KEYENCE CORP.,LT-9000 series) was used. In the peripheral wall portion 17, five placesdifferent in positions in the up-and-down direction 5 were measured. Theresults are shown in Table 1.

TABLE 1 Unit (μm) Periph- Periph- Periph- Periph- Periph- eral eral eraleral eral wall wall wall wall wall Top portion portion portion portionportion portion 1 2 3 4 5 Ex. 1 218 46 48 54 60 72 Ex. 2 224 50 60 68 8198 Ex. 3 224 41 47 58 68 89 Comp. 67 63 78 85 99 129 Ex.[Collapse Test]

Single axial compressive force was applied to the pocket portions 16 ofeach of the PTP sheets 10 according to Examples 1 to 3 and ComparativeExample in the downward direction from the top portion 18 (directiontoward the second sheet 15). Then, the measurement was performed underthe conditions where the force (N) when the second sheet 15 was rupturedwas defined as the upper yield point and the force (N) when thedeformation of the top portion 18 reached up to a region (plane region)other than the pocket portion 16 of the first sheet 14 was defined asthe maximum point. For the measurement, a tablet press-out tester(Shimadzu Corporation, EZ Test) was used. The results are shown in Table2.

TABLE 2 Unit (N) Upper yield point Maximum point Ex. 1 18.9 28.8 Ex. 216.5 44.7 Ex. 3 19.4 35.3 Comp. Ex. 13.7 70.5

As shown in Table 1, in all Examples 1 to 3, the wall thickness of theperipheral wall portion 17 of the pocket portion 16 was smaller than thewall thickness of the top portion 18. On the other hand, in ComparativeExample, most of the wall thickness of the peripheral wall portion 17 ofthe pocket portion 16 tended to be larger than the wall thickness of thetop portion 18 and, in particular, the wall thickness of the peripheralwall portion 17 tended to increase toward the second sheet 15. Moreover,it was confirmed by visual confirmation that the top portion 18 of thepocket portions 16 of each of Examples 1 to 3 had transparency higherthan that of Comparative Example.

As shown in Table 2, the force (N) at the upper yield point in Examples1 to 3 was not different from the force (N) at the upper yield point inComparative Example but the force (N) at the maximum point in Examples 1to 3 was clearly smaller than the force (N) at the maximum point inComparative Example.

[Stability Test]

10 tablets containing losartan potassium and hydrochlorothiazide wereenclosed in the PTP sheets 10 according to Example 1 and ComparativeExample. Each PTP sheet 10 and each PTP sheet 10 were subjected toaluminum pillow packaging, and then stored at 40° C. and 75% RT(Relative Humidity). Then, the proportion of analogous substances (Totalamount and Maximum amount of each substance) contained in the tabletsenclosed in each PTP sheet 10 was measured at the start of the storage,1 month later, 3 months later, and 6 months later. The measurement ofthe analogous substances was performed using liquid chromatography. Thetotal (total amount) of the peak area of the analogous substances, i.e.each substance other than losartan and hydrochlorothiazide, obtained byliquid chromatography, and the peak area (Maximum amount of eachsubstance) which was the maximum among the peak areas of the analogoussubstances were calculated as the ratio (%) to the peak area of thelosartan in the standard solution. The results are shown in Table 3.

TABLE 3 (Unit: %) At start 1 month 3 months 6 months of storage laterlater later Ex. 1 Total 0.06 0.09 0.09 0.43 (without amount aluminumMaximum 0.02 0.03 0.03 0.23 pillow amount of packaging) each substanceComp. EX. Total 0.07 0.09 0.11 0.37 (without amount aluminum Maximum0.03 0.05 0.05 0.13 pillow amount of packaging) each substance Ex. 1(with Total 0.06 0.08 0.09 0.13 aluminum amount pillow Maximum 0.02 0.050.05 0.03 packaging) amount of each substance Comp. EX. Total 0.07 0.080.07 0.12 (with amount aluminum Maximum 0.03 0.04 0.03 0.03 pillowamount of packaging) each substance

As shown in Table 3, regarding the proportion (Total amount and Maximumamount of each substance) of the analogous substances in each PTP sheet10 according to Example 1 and Comparative Example and the proportion(Total amount and Maximum amount of each substance) of the analogoussubstances in each PTP sheet 10 subjected to aluminum pillow packaging,in the comparison between Example 1 and Comparative Example until 6months passed, a considerable difference in the numerical values was notobserved. Thus, it was confirmed that the PTP sheets 10 according toExample 1 and Comparative Example have equivalent airtightness withrespect to the storage stability of pharmaceutical drugs.

REFERENCE SIGNS LIST

-   10 PTP sheet-   11 Solid pharmaceutical drug-   14 First sheet-   15 Second sheet-   16 Pocket portion-   17 Peripheral wall portion-   18 Top portion-   19 Partial region-   31 Upper Surface (First surface)-   32 Lower surface (Second surface)-   33 Peripheral surface (Third surface)-   34 Top surface (Fourth surface)-   51 Concave portion

The invention claimed is:
 1. A method of manufacturing a PTP sheet forpackaging a pharmaceutical drug, comprising: positioning a first flatsheet of fixed thickness between a die and a heating plug, the diehaving a concavity, the heating plug having an annular-shaped endsurface; contacting a partial region of the first flat sheet with theannular-shaped end surface, the annular-shaped end surface of theheating plug imparting heat to a corresponding annular shape at thepartial region; decompressing a concavity of the die by flowing air fromthe concavity; in response to the decompressing sucking a pocket portionof the first flat sheet into the concavity and molding the pocketportion to a shape of the concavity, and extending length of the heatedpartial region during said decompressing and sucking, so that wallthickness of the partial region decreases relative to wall thickness ofa remaining portion of the pocket portion and a portion of the firstsheet surrounding the pocket portion; wherein the PTP sheet comprisesthe first flat sheet and a second sheet, the first flat sheet having asurface for facing the second sheet, the first flat sheet having a firstportion, a second portion, and a third portion, the first portion andsecond portion configured for contacting the second sheet; wherein thethird portion is configured during said sucking and extending steps asthe pocket portion having sidewalls and a base portion, the pocketportion configured for holding the pharmaceutical drug; and wherein thepartial region forms at least a portion of the sidewalls, the sidewallshaving a wall thickness less than the wall thickness of the baseportion, the first portion, and the second portion.
 2. The method ofmanufacturing the PTP sheet according to claim 1, wherein an outer shapeof the pocket portion is a cylindrical shape.
 3. The method ofmanufacturing the PTP sheet according to claim 1, wherein a maincomponent of the first sheet is a thermoplastic resin.
 4. The method ofmanufacturing the PTP sheet according to claim 1, wherein the secondsheet contains aluminum as a main component.
 5. The method ofmanufacturing the PTP sheet according to claim 1, wherein the wallthickness of the sidewalls of the pocket portion is 40 to 160 μm and thewall thickness of the base portion is 200 to 400 μm.
 6. The method ofmanufacturing the PTP sheet according to claim 1, wherein the baseportion has a wall thickness equal to the wall thickness of the firstportion and second portion of the first sheet.